Cerebral ischemia as a consequence of stroke often produces irreversible brain damage and permanent functional disability. There is presently no practical treatment for such ischemic brain injury. Certain neurotrophic proteins have been shown to have beneficial neuroprotective effects when administered after experimental stroke in laboratory animals, but these proteins are unlikely to be useful therapeutic agents. They cannot be delivered expeditiously to stroke-affected brain regions because of exclusion by the blood brain barrier. Neuromedica, Inc. has developed two candidate neuroprotective agents which it feels will be of great practical value in this area. The neuroprotective activity of these agents has been demonstrated in vitro, and evidence indicates that they will gain access to the brain after-systemic administration. This proposal outlines a research program intended to demonstrate the efficacy of these agents in protecting against ischemia-induced brain injury in vivo. Gerbils will be subjected to cerebral ischemia by carotid artery occlusion and treated with NMI's candidate neuroprotective agents. The agents' efficacy will be determined by monitoring behavior known to be influenced by ischemic brain injury and by histological analysis of key regions of the gerbil brains.